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Neuro-navigation is a key technology to ensure the clinical efficacy of TMS. However, the neuro-navigation system based on positioning sensor is currently unable to be promoted and applied in clinical practice due to its time-consuming and high-cost. In the present study, we designed I-Helmet system to promote an individualized and clinically friendly neuro-navigation approach to TMS clinical application. I-Helmet system is based on C++ with a graphical user interface that allows users to design a 3D-printed helmet model for coil navigation. Besides, a dedicated coil positioning accuracy detection method was promoted based on three-dimensional (3D) printing and 3D laser scanning for evaluation. T1 images were collected from 24 subjects, and based on each image, phantom were created to simulate skin and hair. Six 3D-printed helmets with the head positioning hole enlarged by 0–5% tolerance in 1% increments were designed to evaluate the influences of skin, hair, and helmet-tolerance on the positioning accuracy and contact force of I-Helmet. Finally, I-Helmet system was evaluated by comparing its positioning accuracy with three skin hardnesses, three hair styles, three operators, and with or without landmarks. The accuracy of the proposed coil positioning accuracy detection method was about 0.30 mm in position and 0.22° in orientation. Skin and hair had significant influences on positioning accuracy (p 0.05). The tolerance of the helmet presented significant influences on positioning accuracy (p

Background and objectiveIt has been proved that repetitive transcranial magnetic stimulation (rTMS) triggers the modulation of homeostatic metaplasticity, which causes the effect of rTMS to disappear or even reverse, and a certain length of interval between rTMS trains might break the modulation of homeostatic metaplasticity. However, it remains unknown whether the effects of high-frequency rTMS can be modulated by homeostatic metaplasticity by lengthening the train duration and whether homeostatic metaplasticity can be broken by prolonging the inter-train interval.MethodsIn this study, 15 subjects participated in two experiments including different rTMS protocols targeting the motor cortex. In the first experiment, high-frequency rTMS protocols with different train durations (2 s and 5 s) and an inter-train interval of 25 s were adopted. In the second experiment, high-frequency rTMS protocols with a train duration of 5 s and different inter-train intervals (50 s and 100 s) were adopted. A sham protocol was also included. Changes of motor evoked potential amplitude acquired from electromyography, power spectral density, and intra-region and inter-region functional connectivity acquired from electroencephalography in the resting state before and after each rTMS protocol were evaluated.ResultsHigh-frequency rTMS with 2 s train duration and 25 s inter-train interval increased cortex excitability and the power spectral density of bilateral central regions in the alpha frequency band and enhanced the functional connectivity between central regions and other brain regions. When the train duration was prolonged to 5 s, the after-effects of high-frequency rTMS disappeared. The after-effects of rTMS with 5 s train duration and 100 s inter-train interval were the same as those of rTMS with 2 s train duration and 25 s inter-train interval.ConclusionOur results indicated that train duration and inter-train interval could induce the homeostatic metaplasticiy and determine the direction of intensity of rTMS after-effects, and should certainly be taken into account when performing rTMS in both research and clinical practice.

BackgroundNeuroimaging studies have identified aberrant activity patterns in multiple brain regions in functional dyspepsia (FD) patients. However, due to the differences in study design, these previous findings are inconsistent, and the underlying neuropathological characteristics of FD remain unclear.MethodsEight databases were systematically searched for literature from inception to October 2022 with the keywords “Functional dyspepsia” and “Neuroimaging.” Thereafter, the anisotropic effect size signed the differential mapping (AES-SDM) approach that was applied to meta-analyze the aberrant brain activity pattern of FD patients.ResultsA total of 11 articles with 260 FD patients and 202 healthy controls (HCs) were included. The AES-SDM meta-analysis demonstrated that FD patients manifested increased activity in the bilateral insula, left anterior cingulate gyrus, bilateral thalamus, right precentral gyrus, left supplementary motor area, right putamen, and left rectus gyrus and decreased functional activity in the right cerebellum compared to the HCs. Sensitivity analysis showed that all these above regions were highly reproducible, and no significant publication bias was detected.ConclusionThe current study demonstrated that FD patients had significantly abnormal activity patterns in several brain regions involved in visceral sensation perception, pain modulation, and emotion regulation, which provided an integrated insight into the neuropathological characteristics of FD.

Different acupoints exhibiting similar therapeutic effects are a common phenomenon in acupuncture clinical practice. However, the mechanism underlying this phenomenon remains unclear. This study aimed to investigate the similarities and differences in cerebral activities elicited through stimulation of CV12 and ST36, the two most commonly used acupoints, in the treatment of gastrointestinal diseases, so as to partly explore the mechanism of the different acupoints with similar effects. Thirty-eight eligible functional dyspepsia (FD) patients were randomly assigned into either group A (CV12 group) or group B (ST36 group). Each patient received five acupuncture treatments per week for 4 weeks. The Symptom Index of Dyspepsia (SID), Nepean Dyspepsia Symptom Index (NDSI), and Nepean Dyspepsia Life Quality Index (NDLQI) were used to assess treatment efficacy. Functional MRI (fMRI) scans were performed to detect cerebral activity changes at baseline and at the end of the treatment. The results demonstrated that (1) improvements in NDSI, SID, and NDLQI were found in both group A and group B (p < 0.05). However, there were no significant differences in the improvements of the SID, NDSI, and NDLQI scores between group A and group B (p > 0.05); (2) all FD patients showed significantly increased amplitude of low-frequency fluctuation (ALFF) in the left postcentral gyrus after acupuncture treatment, and the changes of ALFF in the left postcentral gyrus were significantly related to the improvements of SID scores (r = 0.358, p = 0.041); and (3) needling at CV12 significantly decreased the resting-state functional connectivity (rsFC) between the left postcentral gyrus and angular gyrus, caudate, middle frontal gyrus (MFG), and cerebellum, while needling at ST36 significantly increased the rsFC between the left postcentral gyrus with the precuneus, superior frontal gyrus (SFG), and MFG. The results indicated that CV12 and ST36 shared similar therapeutic effects for dyspepsia, with common modulation on the activity of the postcentral gyrus in FD patients. However, the modulatory pattern on the functional connectivity of the postcentral gyrus was different. Namely, stimulation of CV12 primarily involved the postcentral gyrus–reward network, while stimulation of ST36 primarily involved the postcentral gyrus–default mode network circuitry.

Acupuncture is an effective therapy for functional dyspepsia (FD). However, the efficacy of acupuncture in the treatment of FD varies among individuals in clinical practice. This study aimed to reveal the brain response patterns in acupuncture higher response/lower response FD patients. Firstly, we performed a within-group comparison of brain function activity before and after acupuncture treatment in 115 FD patients and analyzed the correlation between brain function activity changes and clinical improvements. Secondly, 115 subjects were divided into the acupuncture higher response group or the lower response group based on the median clinical improvement values. The changes in functional brain activity after acupuncture treatment were investigated in these two groups, respectively. Finally, the identified brain regions associated with the clinical improvements were set as regions of interest (ROI), and the ROI-to-voxel functional connectivity comparisons were also performed in both groups, respectively. The results demonstrated that the functional activities of the left cerebellum inferior, right middle temporal gyrus, and right medial prefrontal cortex (mPFC) were increased, and the left Heschl and right middle cingulate cortex were decreased in 115 FD patients after acupuncture treatment. The functional connectivity changes of mPFC were correlated with improving the Nepean Dyspepsia Symptom Index. The significant increase in mPFC functional activity was also found in acupuncture higher response FD patients but not in lower response FD patients. The functional connectivity between the mPFC and default mode network (DMN) was significantly diminished in the higher response group but not in the lower response group. In conclusion, this study suggested that modulating the functional activity of the mPFC and its connectivity to the DMN may be one of the important mechanisms of acupuncture for treating FD with a higher response.

Objectives: This study was conducted in order to investigate the study design and main outcomes of acupuncture neuroimaging studies on low back pain (LBP).Methods: Neuroimaging studies of acupuncture on LBP were collected from three English databases such as PubMed and four Chinese databases such as China National Knowledge Infrastructure (CNKI) from inception to December 31, 2020. Study selection, data extraction, and assessment of risk of bias were performed independently by two investigators. The quality of studies was appraised with the Cochrane's risk of bias tools. Information on basic information, methodology, and brain imaging data were extracted.Results: The literature search returned 310 potentially eligible studies and 19 articles met inclusion criteria; 78.9% of studies chose manual acupuncture as the intervention, 89.5% of studies evaluated functional changes elicited by acupuncture, and 68.4% of studies used resting-state fMRI as imaging condition. The most frequently reported acupuncture-induced brain alterations of LBP patients were in the prefrontal cortex, insula, cerebellum, primary somatosensory cortex, and anterior cingulate cortex. There was a significant correlation between improved clinical outcomes and changes in the brain.Conclusions: The results suggested that improving abnormal structure and functional activities in the brain of the LBP patient is an important mechanism of acupuncture treatment for LBP. The brain regions involved in acupuncture analgesia for LBP were mainly located in the pain matrix, default mode network (DMN), salience network (SN), and descending pain modulatory system (DPMS). However, it was difficult to draw a generalized conclusion due to the heterogeneity of study designs. Further well-designed multimodal neuroimaging studies investigating the mechanism of acupuncture on LBP are warranted.

IntroductionIn this retrospective study, resting-state functional connectivity (FC) in patients with migraine was analyzed to identify potential pathological pain processing patterns and compared them to those in healthy controls (HCs). The FC patterns in patients between pre- and post-acupuncture sessions were also analyzed to determine how acupuncture affects neurological activity and pain perception during the migraine interictal period.MethodsIn total, 52 patients with migraine without aura (MwoA) and 60 HCs were recruited. Patients with migraine were given acupuncture treatment sessions for 4 weeks. As a primary observation, functional magnetic resonance images were obtained at the beginning and end of the sessions. HCs received no treatment and underwent one functional magnetic resonance imaging (fMRI) scan after enrollment. After the fMRI data were preprocessed, a region of interest (ROI)-to-ROI analysis was performed with predefined ROIs related to pain processing regions.ResultsThe first analysis showed significantly different FCs between patients with MwoA and HCs [false discovery rate corrected p-value (p-FDR) < 0.05]. The FCs were found to be mainly between the cingulate gyrus (CG) and the insular gyrus, the CG and the inferior parietal lobule (IPL), the CG and the superior frontal gyrus, and the middle frontal gyrus and the IPL. The second analysis indicated that acupuncture treatment partly restored the different FCs found in the first analysis (p-FDR < 0.05). Furthermore, subgroup analysis found different brain activity patterns in headache-intensity restored condition and headache-frequency restored condition. Lastly, the correlation analysis suggested a potential correlation between FCs and clinical symptoms (p < 0.05).ConclusionThis study suggests that pain processing is abnormal in migraine, with significantly abnormal FCs in the frontal, parietal, and limbic regions. This finding could be a typical pathological feature of migraine. Acupuncture has been identified to relieve headache symptoms in two ways: it restores the pain processing function and regulates pain perception.

IntroductionMigraine without aura (MwoA) is a primary type of migraine, a common disabling disorder, and a disabling neurological condition. The headache is a complex experience, a common form of pain, in which multiple sensory information dimensions are combined to provide a unified conscious event. Migraine ictal have unique neuroimage biomarkers, but the brain is also affected during the inter-ictal phase. According to the current studies, a hypothesis was constructed that the altered integration of pain spatial and intensity information impacts headache intensity in the inter-ictal period.MethodsIn this study, we applied theory-based region-to-region functional connectivity (FC) analyses to compare the differences in resting-state FC between MwoA participants and healthy controls with the pain integration hypothesis. After the correlation matrices between FC edges and clinical symptoms were constructed, the moderating effect and simple slope tests were investigated to explain whether and how the dysfunction of pain features discrimination affects the clinical symptoms.ResultsFunctional connectivity analyses showed significantly decreased FC edges between the left dorsolateral superior frontal gyrus (SFGdor) and left insula, and an increased FC edge between the left SFGdor and bilateral angular gyrus. The correlation matrix showed no significant correlation between significantly altered FC edge and headache duration, frequency, Zung self-rating anxiety scale, and Zung self-rating depression scale. Only one significantly altered edge in the MwoA condition was significantly correlated with headache intensity. Moderating Module 1 and 2 manifested the moderator variable (altered rs-FC edge) moderated the link between the normal edges and headache intensity.ConclusionThe pain features integration processes in migraineurs vary from HCs, related to the clinical symptoms during a migraine attack. Moreover, the clinical symptoms will be affected by one or more discrimination modules. And the spatial or intensity discrimination modules have a higher impact when combined with another module on clinical symptoms than the single module.

Transcranial electrical stimulation is an important neuromodulation tool, which has been widely applied in the cognitive sciences and in the treatment of neurological and psychiatric diseases. In this work, a novel non-invasive method of transcranial electrical stimulation with high-resolution transcranial magneto-acoustic stimulation (TMAS) method has been tested experimentally in living mice for the first time. It can achieve spatial resolution of 2 mm in the cortex and even in the deep brain regions. The induced electrical field of TMAS was simulated and measured using a test sample. Then, an animal experimental system was built, and the healthy as well as Parkinson’s disease (PD) mice were simulated by TMAS in vivo. To investigate the effect of transcranial ultrasound stimulation (TUS) at the same time as TMAS, a TUS group was added in the experiments and its results compared with those of the TMAS group. The results not only demonstrate the high-resolution ability and safety of TMAS, but also show that both TMAS and TUS improved the synaptic plasticity of the PD mice and might improve the spatial learning and memory ability of the healthy mice and the PD mice, although the improvement performance of the TMAS group was superior to that of the TUS-group. Based on the in vivo TMAS studies, we propose that TMAS functions as a dual-mode stimulation combining the electric field of the magneto-acoustic effect and the mechanical force of TUS. Our results also provide an explanation of the mechanism of TMAS. This research suggests that future use of US stimulation in magnetic resonance imaging (MRI)-guided studies should involve careful consideration of the induced magneto-acoustic electrical field caused by the static magnetic field of MRI.